engleski

Correlation of cognitive deficits and brain cholinesterase activity in streptozotocin- intracerebroventricularly treated rat model of sporadic Alzheimer's disease

Background. Cholinergic deficits in the brain play important role in the pathophysiology of cognitive deficits in sporadic Alzheimer’s disease (sAD). Rats treated intracerebroventricularly with streptozotocin (STZ-icv), have been proposed as an experimental sAD model. Increased brain cholinesterase activity and cognitive deficits in this model have been followed in literature up to 1 and 3 months after the STZ-icv injection, respectively. Objective. We investigated the effect of three STZ-icv doses on cognitive functions and brain cholinesterase activity in the STZ-icv rat model, three months after the STZ-icv administration. Methods. Adult Wistar rats were STZ-icv treated with 0.3, 1 and 3 mg/kg dose. Measurements of (1) cognitive deficits (Morris Water Maze /MWM/ and Passive Avoidance /PA/ tests), (2) cholinesterase activity in hippocampus (HPC) and parietotemporal cortex (PTC) (Elman’s method), (3) amyloid precursor protein mRNA (APP) expression (RT-PCR) and amyloid β (Aβ) accumulation (Aβ immunohistochemistry), were explored 3 months after STZ-icv administration. Data were analyzed by Cruscal-Walles ANOVA and Mann-Whitney U test (P<0.05). Results. STZ-icv (1 and 3 mg/kg) treated rats demonstrated memory retention deficits (PA: -46% and -66%, MWM: -36% and -38%, respectively, p<0.05). STZ-icv 3 mg/kg dose caused a mild (+15%), insignificant (p=0.09) increase in HPC cholinesterase activity. Positive Aβ signal was found in cerebral capillary walls of STZ-icv treated rats with no changes in APP mRNA production. Conclusion. Three months after STZ-icv administration, rat sAD model develops marked dose-dependent cognitive deficits, which are followed by only mildly changed brain cholinesterase activity. In contrast to that, three months after ST-icv administration, this model develops cerebral Aβ angiopathy which does not seem to be caused by increased Aβ production. Supported by UKF, DAAD and MZOS.

cholinesterase; amyloid beta; streptozotocin

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